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phosphatidylserine, multiple sclerosis

Dana Ben-Ami Shor, Guy A Weiss, Ori Barzilai, Maya Ram, Juan-Manuel Anaya, Yehuda Shoenfeld, Yaniv Sherer
BACKGROUND: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. OBJECTIVES: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS. METHODS: Using the BioPlex 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls...
September 2015: Israel Medical Association Journal: IMAJ
Reid A Roberts, Timothy K Eitas, James D Byrne, Brandon M Johnson, Patrick J Short, Karen P McKinnon, Shannon Reisdorf, J Christopher Luft, Joseph M DeSimone, Jenny P Ting
The possibility of engineering the immune system in a targeted fashion using biomaterials such as nanoparticles has made considerable headway in recent years. However, little is known as to how modulating the spatial presentation of a ligand augments downstream immune responses. In this report we show that geometric manipulation of phosphatidylserine (PS) through fabrication on rod-shaped PLGA nanoparticles robustly dampens inflammatory responses from innate immune cells while promoting T regulatory cell abundance by impeding effector T cell expansion...
December 2015: Biomaterials
Dominique F Leitner, Bozho Todorich, Xuesheng Zhang, James R Connor
We have previously established that T cell immunoglobulin and mucin domain containing 2 (Tim2) is an H-ferritin receptor on oligodendrocytes (OLs). Tim2 also binds Semaphorin4A (Sema4A). Sema4A is expressed by lymphocytes, and its role in immune activation is known; however, its relationship to diseases that are known to have myelin damage has not been studied. In this study, we demonstrate that Sema4A is cytotoxic to OLs in culture: an effect accompanied by process collapse, membrane blebbing, and phosphatidylserine inversion...
May 2015: ASN Neuro
Markus Arnold, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: Mitoxantrone, a cytotoxic drug used for the treatment of malignancy and multiple sclerosis, is at least in part effective by triggering apoptosis. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a type of suicidal cell death. Hallmarks of eryptosis are cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signalling involved in eryptosis include Ca(2+)-entry, ceramide formation and oxidative stress...
2014: Cellular Physiology and Biochemistry
Jeroen F J Bogie, Winde Jorissen, Jo Mailleux, Philip G Nijland, Noam Zelcer, Tim Vanmierlo, Jack Van Horssen, Piet Stinissen, Niels Hellings, Jerome J A Hendriks
BACKGROUND: Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. RESULTS: We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ)...
2013: Acta Neuropathologica Communications
Gloudina M Hon, Mogamat S Hassan, Susan J van Rensburg, Stefan Abel, Rajiv T Erasmus, Tandi Matsha
Immune cell membrane lipids are important determinants of membrane fluidity, eicosanoid production and phagocytosis and fatty acid metabolic abnormalities have been reported in immune cells from patients with multiple sclerosis. The aim of this study was to investigate the relationship between peripheral blood mononuclear cell membrane fluidity, permeability status, and disease outcome as measured by the Kurtzke expanded disability status scale. Phospholipids, fatty acids and cholesterol composition in peripheral blood mononuclear cells from 26 patients diagnosed with multiple sclerosis and 25 healthy control subjects were determined by colorimetric assay, gas chromatography and enzymatic assays, respectively...
March 2012: Indian Journal of Hematology & Blood Transfusion
Sabrina Grecchi, Giuliano Mazzini, Antonella Lisa, Marie-Therese Armentero, Roberto Bergamaschi, Alfredo Romani, Fabio Blandini, Carol Di Perri, Anna Ivana Scovassi
Multiple Sclerosis (MS) is a chronic disease of the central nervous system, the etiology of which, although not completely known, involves inflammation and autoimmunity. In the present study we aimed at identifying molecular markers of apoptosis, cellular stress and DNA damage in isolated peripheral blood mononuclear cells (PBMCs) of MS patients. The analysis was carried on 19 relapsing-remitting untreated MS patients and 13 healthy individuals. We investigated the emergency-driven synthesis of poly(ADP-ribose) (PAR), the expression level of the constitutive enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the DNA damage-induced phosphorylation of histone H2AX...
2012: PloS One
Sukhvir Chand, Nisha Mehta, Malkeet Singh Bahia, Anshuman Dixit, Om Silakari
PKC-θ is a serine/threonine specific protein kinase and its activation depends upon the concentration of diacylglycerol (DAG) and phospholipids (phosphatidylserine). PKC-θ phosphorylates a variety of proteins that are known to be involved in the diverse cellular signaling pathways. It is predominantly expressed in the T-cells and localized in the center of immunological synapse upon T-cell receptor (TCR) and CD28 signaling. Activation of PKC-θ leads to the activation of various transcription factors in the nuclei of T-cells, e...
2012: Current Pharmaceutical Design
Peggy P Ho, Jennifer L Kanter, Amanda M Johnson, Hrishikesh K Srinagesh, Eun-Ju Chang, Timothy M Purdy, Keith van Haren, William R Wikoff, Tobias Kind, Mohsen Khademi, Laura Y Matloff, Sirisha Narayana, Eun Mi Hur, Tamsin M Lindstrom, Zhigang He, Oliver Fiehn, Tomas Olsson, Xianlin Han, May H Han, Lawrence Steinman, William H Robinson
Lipids constitute 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain, and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives...
June 6, 2012: Science Translational Medicine
Seung-Chul Choi, Venkateswara R Simhadri, Linjie Tian, Aleksandra Gil-Krzewska, Konrad Krzewski, Francisco Borrego, John E Coligan
Reportedly, CD300f negatively regulates interactions between dendritic and T cells and acts as an anti-inflammatory molecule in a multiple sclerosis mouse model. We found that a CD300f/Fc chimeric protein specifically binds to apoptotic/dead splenocytes and to apoptotic cells from starved or irradiated lymphocytic cell lines, an observation extended to insect cells. CD300f also binds PMA/ionomycin-activated splenocytes and Ag-stimulated T cells, an interaction inhibited by Annexin V. By ELISA, cosedimentation, and surface plasmon resonance using phospholipid-containing liposomes, we show that CD300f preferentially binds phosphatidylserine and requires a metal ion...
October 1, 2011: Journal of Immunology: Official Journal of the American Association of Immunologists
Majid Assadi, Reza Nemati, Iraj Nabipour, Hooman Salimipour, Abdullatif Amini
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that involves myelin, oligodendrocytes and axons and culminates in consecutive neuronal death and progressive neurologic disability. Based on magnetic resonance imaging (MRI), neuroaxonal loss in MS results in brain atrophy and has a strong correlation with neurological disability. The newer MR imaging tools seem to be sensitive biomarkers for measuring the pathogenetic processes associated with disease activity and progression...
July 2011: Medical Hypotheses
Gloudina Hon, Mogamat Hassan, Susan Janse van Rensburg, Stefan Abel, De Wet Marais, Paul van Jaarsveld, Cornelius Smuts, Franclo Henning, Rajiv Erasmus, Tandi Matsha
Measurement of fatty acids in biological fluids and cell membranes including leucocytes from multiple sclerosis patients is inconsistent. The objective of the present study was to investigate the fatty acid composition within the different membrane phospholipid fractions in peripheral blood mononuclear cells in multiple sclerosis patients, and correlate with severity of neurological outcome as measured by the Kurtzke Expanded Disability Status Scale and Functional System Scores. The fatty acid composition of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin and phosphatidylinositol phospholipids in the peripheral blood mononuclear cells of twenty-six multiple sclerosis and twenty-five control subjects were measured by GC, and C-reactive protein was measured in all subjects...
November 2009: British Journal of Nutrition
Gilles N Chironi, Chantal M Boulanger, Alain Simon, Françoise Dignat-George, Jean-Marie Freyssinet, Alain Tedgui
Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury, and/or apoptosis. The measurement of the phospholipid content (mainly phosphatidylserine; PSer) of microparticles and the detection of proteins specific for the cells from which they are derived has allowed their quantification and characterization. Microparticles of various cellular origin (platelets, leukocytes, endothelial cells) are found in the plasma of healthy subjects, and their amount increases under pathological conditions...
January 2009: Cell and Tissue Research
Abdiwahab A Musse, Eugenia Polverini, Reinout Raijmakers, George Harauz
Multiple sclerosis is a complex human neurodegenerative disease, characterized by the active destruction of the insulating myelin sheath around the axons in the central nervous system. The physical deterioration of myelin is mediated by hyperdeimination of myelin basic and other proteins, catalysed by the Ca2+ -dependent enzyme peptidylarginine deiminase 2 (PAD2). Thus, inhibition of PAD2 may be of value in treatment of this disease. Here, we have first characterized the in vitro kinetic properties of the human peptidylarginine deiminase isoform 2 (hPAD2)...
October 2008: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Yayoi Nagai, Akira Shimizu, Osamu Ishikawa
We report a 32-year-old woman with a 12-year history of systemic lupus erythematosus. Physical examination revealed indurated plaques with small ulcers on her extremities and trunk, which were histologically diagnosed as lupus erythematosus profundus. On her arms and knees, multiple small calcified nodules were noted in the dermis and subcutis. An elevated level of anti-phosphatidylserine/prothrombin antibodies was noted. She had been suffering from digital ulcers on the left fourth finger. Despite conservative therapies, new ulcers appeared on other fingers...
July 2008: Journal of Dermatology
Dorothy D Wood, Cameron A Ackerley, Ben van den Brand, Li Zhang, Reinout Raijmakers, Fabrizio G Mastronardi, Mario A Moscarello
An understanding of the structure and composition of the myelin sheath is essential to understand the pathogenesis of demyelinating diseases such as multiple sclerosis (MS). The presence of citrulline in myelin proteins in particular myelin basic protein (MBP) causes an important change in myelin structure, which destabilizes myelin. The peptidylarginine deiminases (PADs) are responsible for converting arginine in proteins to citrulline. Two of these, PAD2 and PAD4, were localized to the myelin sheath by immunogold electron microscopy...
April 2008: Laboratory Investigation; a Journal of Technical Methods and Pathology
Carlos J Bidot, Lawrence L Horstman, Wenche Jy, Joaquin J Jimenez, Carlos Bidot, Yeon S Ahn, J Steven Alexander, Eduardo Gonzalez-Toledo, Roger E Kelley, Alireza Minagar
BACKGROUND: The presence of antiphospholipid antibodies (APLA) in multiple sclerosis (MS) patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA. METHODS: A consecutive cohort of 24 subjects with relapsing-remitting (RR) MS were studied of whom 7 were in remission (Rem) and 17 in exacerbation (Exc)...
2007: BMC Neurology
P Rispoli, R Carzino, T Svaldo-Lanero, A Relini, O Cavalleri, A Fasano, G M Liuzzi, G Carlone, P Riccio, A Gliozzi, R Rolandi
Myelin basic protein (MBP) is a major protein of the myelin membrane in the central nervous system. It is believed to play a relevant role in the structure and function of the myelin sheath and is a candidate autoantigen in demyelinating processes such as multiple sclerosis. MBP has many features typical of soluble proteins but is capable of strongly interacting with lipids, probably via a conformation change. Its structure in the lipid membrane as well as the details of its interaction with the lipid membrane are still to be resolved...
September 15, 2007: Biophysical Journal
Neeta Garg, Robert Zivadinov, Murali Ramanathan, Irene Vasiliu, Jaclyn Locke, Kelly Watts, Jordan Lema, Jyotsna Rajeswary, Frederick E Munschauer, Julian Ambrus, Bianca Weinstock-Guttman
BACKGROUND: Autoreactive antibodies (ARAB) occur more frequently in patients with multiple sclerosis (MS) than in general population and the presence of these antibodies often causes uncertainty regarding the disease course, response to therapy and the diagnosis of MS. METHODS: Retrospective analyses of the ARAB, clinical and MRI data of a consecutive patient cohort of MS and clinically isolated syndrome (CIS) patients were conducted. The patients were evaluated for an extensive panel that included various subtypes of antiphospholipid antibody (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine (APS), anti-beta-2-glycoprotein-1 (ABGP), anti-cardiolipin (ACA), and several other ARAB such as antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), anti-thyroid peroxidase antibodies (ATA), anti-SS-A, and anti-SS-B antibodies...
July 2007: Journal of Neuroimmunology
N Garg, B Weinstock-Guttman, K Bhasi, J Locke, M Ramanathan
Approximately 5-25% of interferon-beta (IFN-beta) treated multiple sclerosis (MS) patients develop anti-IFN-beta neutralizing antibodies (NAb) but the patient-specific variables associated with the risk of developing anti-IFN-beta antibodies are poorly understood. Anti-IFN-beta NAb are a subset of anti-IFN-beta binding antibodies (BAb) and all patients with NAb generally have high levels of associated BAb. The purpose of this research was to assess the association between autoreactive antibodies (ARAB) and the risk of developing anti-IFN-beta BAb in MS patients...
August 2007: Multiple Sclerosis: Clinical and Laboratory Research
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